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含双(2-羟乙基)乙二胺的异双金属配位化合物对HT29、HeLa、C6和Vero细胞的药理活性评价

Evaluation of Pharmacological Activity of Heterobimetallic Coordination Compounds Containing -Bis (2-hydroxyethyl)-Ethylenediamine on HT29, HeLa, C6 and Vero cells.

作者信息

Aydin Ali, Korkmaz Şengül Aslan

机构信息

Faculty of Art and Science, Department of Molecular Biology and Genetics, Gaziosmanpaşa University, 60240, Tokat, Turkey.

Faculty of Engineering, Department of Bioengineering, Munzur University, 62000, Tunceli, Turkey.

出版信息

Iran J Pharm Res. 2019 Fall;18(4):2011-2027. doi: 10.22037/ijpr.2019.1100854.

Abstract

The present study was conducted in order to investigate the pharmacological activities of three heterobimetallic coordination compounds: [Cd(-bishydeten)][Ni(CN)] (), [Cu(-bishydeten)Co(CN)].3HO (), and K[Cd(-bishydeten)Co(CN)].1.5HO () (-bishydeten = -bis(2-hydroxyethyl)-ethylenediamine). This paper describes the ability of complexes to inhibit cell growth, cell migration and human topoisomerase I and to interact with DNA/BSA; this paper also evaluates the potential mechanisms of action exhibited by these compounds via the use of powerful measurement techniques. Studies on HT29, HeLa, C6 and Vero cells revealed that each compound demonstrated significant antiproliferative activity in conjunction with regressed cell migration velocity and caused apoptotic changes in morphology. There are strong data suggesting that the mechanisms of action exhibited by these compounds are associated with their DNA/BSA binding features. The IC and binding constant range for the compounds are 20-180 µM and 1.2-3.2 x 10 M, respectively. Moreover, we observed that these compounds alter the P53-Bcl-2 ratio and inhibit the relaxation activity of human topoisomerase I. Furthermore, a correlation between the antiproliferative effects of these compounds and their cytotoxic activity was observed. In conclusion, preliminary information demonstrates that these compounds have been found to exhibit effective antiproliferative activity against cancer cell lines, indicating that they are a potent candidate for further pharmacological study.

摘要

本研究旨在探究三种异双金属配位化合物的药理活性

[Cd(-bishydeten)][Ni(CN)] ()、[Cu(-bishydeten)Co(CN)].3HO ()和K[Cd(-bishydeten)Co(CN)].1.5HO ()(-bishydeten = -双(2-羟乙基)-乙二胺)。本文描述了这些配合物抑制细胞生长、细胞迁移以及人拓扑异构酶I的能力,以及与DNA/BSA相互作用的能力;本文还通过使用强大的测量技术评估了这些化合物所表现出的潜在作用机制。对HT29、HeLa、C6和Vero细胞的研究表明,每种化合物都表现出显著的抗增殖活性,同时细胞迁移速度降低,并导致细胞形态发生凋亡变化。有强有力的数据表明,这些化合物所表现出的作用机制与其DNA/BSA结合特性有关。这些化合物的IC和结合常数范围分别为20 - 180 µM和1.2 - 3.2 x 10 M。此外,我们观察到这些化合物改变了P53 - Bcl - 2比率,并抑制了人拓扑异构酶I的松弛活性。此外,还观察到这些化合物的抗增殖作用与其细胞毒性活性之间存在相关性。总之,初步信息表明,已发现这些化合物对癌细胞系表现出有效的抗增殖活性,表明它们是进一步药理研究的有力候选物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1de9/7059045/b2371eaed9a1/ijpr-18-2011-g001.jpg

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